The cyclic ADP ribose antagonist 8-NH2-cADP-ribose blocks cholecystokinin-evoked cytosolic Ca2+ spiking in pancreatic acinar cells.
In order to investigate the possible involvement of cyclic ADP ribose as an intracellular messenger for hormone-evoked cytosolic Ca2+ signalling, we performed experiments on intracellularly perfused mouse pancreatic acinar cells. Both a stable inositol 1,4,5 trisphosphate analogue (IP3) and cyclic ADP ribose (cADPR) evoked regular spikes of Ca2+ dependent ion current, reflecting cytosolic Ca2+ spiking. The effect of cADPR, but not IP3, was abolished by the presence intracellularly of the cADPR antagonist 8-NH2-cADPR. External application of cholecystokinin (CCK) in a physiological concentration (2.5-5 pM) evoked a mixture of short-lasting and longer-lasting spikes of Ca2+-dependent ion current. These effects were abolished by the presence intracellularly of 8-NH2-cADPR (18 muM). Increasing the CCK concentration to 15 pM could overcome the inhibition by 18 muM of the antagonist. These experiments provide fresh evidence for the involvement of cADPR receptors in the hormone-evoked cytosolic Ca2+ signalling process in pancreatic acinar cells.
Cancela
J M
JM
The MRC Secretory Control Research Group, The Physiological Laboratory, The University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Petersen
O H
OH
D000200:Action Potentials / Q000187:drug effects; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002766:Cholecystokinin / Q000494:pharmacology*; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques
D036563:Cyclic ADP-Ribose; C082175:8-aminoadenosine cyclic 3',5'-(hydrogen phosphate) 5'-ribofuranosyl ester; D000246:Adenosine Diphosphate Ribose; D015544:Inositol 1,4,5-Trisphosphate; D002766:Cholecystokinin; D002118:Calcium